Study of NOV-002 in Combination With Chemotherapy to Treat Lung Cancer

Phase 3 Trial, Randomized, Open-Label, of NOV-002 in Combination With Paclitaxel and Carboplatin vs. Paclitaxel and Carboplatin Alone for the Treatment of Advanced Non-Small-Cell Lung Cancer (NSCLC)

The purpose of this clinical trial is to find out whether or not the combination of NOV-002 with chemotherapy (paclitaxel and carboplatin) is better at improving overall survival time when compared to chemotherapy alone in people with non-small cell lung cancer (NSCLC).

Earlier clinical trials in NSCLC showed that patients treated with NOV-002 in combination with chemotherapy had a better response (their tumors got smaller in one United States Phase 1/2 trial) than patients who received chemotherapy alone; and in two Phase 2 trials done in Russian patients, at the end of one year, patients treated with NOV-002 with chemotherapy had a better survival rate than patients who did not receive NOV-002 with their chemotherapy.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: NOV-002; Drug: Carboplatin

Detailed Description

NSCLC is a widespread disease with extremely high mortality and morbidity. Even the most widely accepted standard of care chemotherapy in advanced NSCLC, platinum-based doublets, are only palliative, providing marginal efficacy as measured by survival. In addition, such chemotherapy is accompanied by severe, sometimes life-threatening, toxicities which often limit its application. Thus, there is a clear need for new, more effective and safer therapies for advanced NSCLC. In Phase 2 trials, NOV-002 demonstrated a higher response rate and improved survival compared to chemotherapy alone in patients with advanced NSCLC, and was well-tolerated in this patient group. Thus, we are conducting a large Phase 3 trial of NOV-002 to better define its clinical profile and potential benefit in advanced NSCLC patients.

The overall design of this Phase 3 trial reflects major elements of the previous Russian and US clinical trials in advanced NSCLC - it is an open label, randomized controlled trial comparing NOV-002 in combination with first-line chemotherapy (paclitaxel + carboplatin) to first-line chemotherapy alone. Furthermore, it is designed and powered to be a pivotal, registrational trial, sufficient for approval. As its primary efficacy endpoint, this Phase 3 trial aims to demonstrate that the combination of NOV-002 with paclitaxel and carboplatin results in improved overall survival when compared with paclitaxel and carboplatin alone. In addition, several secondary efficacy endpoints will be assessed, including progression free survival, tumor response rate and duration of response, quality of life, myelosuppression and immunomodulation. Overall survival was chosen as the primary endpoint of this trial in the context of FDA (Draft) Guidance ("Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics", April 2005). This Guidance indicates that an improvement in overall survival should be evaluated in randomized controlled trials and is of unquestioned clinical benefit. It indicates that the endpoint is precise and easy to measure, documented by the date of death, and states that bias is not a factor in endpoint measurement, and blinding is not essential. This Phase 3 randomized, controlled, open-label trial thus conforms to this Guidance.

• Study Type: Interventional
• Enrollment (Actual): 903
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6W 2Z8
      • William Osler Health Center
    • Weston, Ontario, Canada, M9N 1N8
      • Humber River Regional Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T1E2
      • Jewish General Hospital
    • Sainte-Foy, Quebec, Canada, G1V 4G5
      • Laval Hospital
• Israel
  • Ashkelon, Israel, 78306
    • Barzilai Medical Center
  • Haifa, Israel, 31096
    • Lin Clinic
  • Kfar-Saba, Israel, 44281
    • Meir Medical Center
  • Petach Tikva, Israel, 49100
    • Institute of Oncology
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
  • Zerifin, Israel, 70300
    • Assaf Harofeh Hospital
• Italy
  • Bergamo, Italy, 24100
    • Azienda Ospedaliera Treviglio Caravaggio
  • Firenze, Italy, 50139
    • Azienda Ospedaliera Careggi
  • Sondrio, Italy, 23100
    • Sondrio Hospital
• Poland
  • Bystra, Poland, 43-360
    • Oddzial Pulmonologiczny z Pododdzialem Chemioterapii
  • Gdansk, Poland, 80-952
    • Samodzielny Publiczny Szpital Kliniczny N°.1
  • Gdynia, Poland, 81-519
    • Oddzial Chemioterapii Pomorskie Centrum Onkologii,
  • Lodz, Poland, 93-513
    • Katedra Onkologii Akademii Medycznej w Lodzi
  • Olsztyn, Poland, 10-228
    • Oddzial Chemioterapii Zaklad Opieki Zdrowotnej MSWiA
  • Otwock, Poland, 05-400
    • Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy Oddzial III
  • Poznan, Poland, 60-659
    • Wielkopolskie Centrum Chorob
  • Prabuty, Poland, 82-550
    • Oddzial Gruzlicy I Chorob Pluc I P
  • Warsaw, Poland, 02-781
    • Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie w Warszawie
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie
• Romania
  • Bucharest, Romania, 022328
    • Institute of Oncology, Department of Medical Oncology II
  • Cluj-Napoca, Romania, 400015
    • Institute of Oncology Cluj-Napoca
  • Cluj-Napoca, Romania, 400015
    • Institute of Oncology, Cluj-Napoca
  • Craiova, Romania, 200642
    • Craiova Emergency Clinical County Hospital
  • Timis County
    • Timisoara, Timis County, Romania, 300239
      • S.C. Oncomed SRL
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Regional Clinical Oncology Center
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Oncology Center, Chemotherapy Department
  • Kazan, Russian Federation, 420029
    • Clinical Oncology Center, Chemotherapy Department
  • Omsk, Russian Federation, 644013
    • Omsk Regional Clinical Oncology Center
  • Orenburg, Russian Federation, 460021
    • Orenburg Regional Clinical Oncology Center
  • Pyatigorsk, Russian Federation, 357500
    • Stavropol Regional Clinical Oncology Center
  • Sochi, Russian Federation, 354057
    • Oncology Center, Hematology Department
  • St. Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital, Department of Thoracic Surgery
  • St. Petersburg, Russian Federation, 194354
    • City General Hospital #2, City Center of Intensive Pulmonology and Thoracic Surgery
  • St. Petersburg, Russian Federation, 197022
    • St. Petersburg Pavlov State Medical University under the Federal Agency for Healthcare and Social Development
  • St. Petersburg, Russian Federation, 198255
    • City Clinical Oncology Center, Thoracic Department
  • Stavropol, Russian Federation, 355047
    • Stavropol Regional Clinical Oncology Center, Chemotherapy Department
  • Tambov, Russian Federation, 390013
    • Tambov Regional Oncology Center, Chemotherapy Department
  • Tatarstan, Russian Federation, 420111
    • Kazan Oncology Center
  • Voronezh, Russian Federation, 394000
    • Voronezh Regional Clinical Oncology Center
• Serbia
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center Bezanijska Kosa
  • Nis, Serbia, 18000
    • Clinical Center Nis, Clinic for Lung Diseases "Knez Selo"
  • Sremska Kamenica, Serbia, 21204
    • Institute of Lung Diseases Sremka Kamenica
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Terrassa, Spain, 08221
    • Hospital Mutua De Terrassa
• Switzerland
  • Sursee, Switzerland, CH 6210
    • Kantonales Spital Sursee-Wolhusen
• Ukraine
  • Cherkassy, Ukraine, 18009
    • Cherkasy Regional Oncology Center
  • Chernihiv, Ukraine, 14029
    • Public Treatment and Prophylaxis Institution: Chernihiv Regional Oncology Center
  • Dnipropetrovsk, Ukraine, 49102
    • City General Hospital #4
  • Ivano-Frankivsk, Ukraine, 76014
    • Regional Oncological Center
  • Kharkiv, Ukraine, 61024
    • S.P. Grigoryev Institute of Medical Radiology
  • Kyiv, Ukraine, 03022
    • Oncology Institute under the Ukrainian Academy of Medical Sciences
  • Simferopol, Ukraine, 95023
    • Crimean Republican Clinical Oncology Center
  • Uzhorod, Ukraine, 88014
    • Zakarpatsky Regional Oncological Clinical Center
• United Kingdom
  • Nottingham, United Kingdom, NG51PB
    • Oncology Research, Nottingham City Hospital
  • Poole, United Kingdom, BH152JB
    • Dorset Cancer Centre, Poole Hospital
  • Somerset, United Kingdom, BA214AT
    • Yeovil District Hospital NHS Foundation Trust, Higher Kingston
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Anchor Unit, Aberdeen Royal Infirmary
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Ninewells Hospital and Medical School Department of Cancer Medicine
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • St. Luke's Cancer Centre
• United States
  • Alabama
    • Muscle Shoals, Alabama, United States, 35661
      • Northwest Alabama Cancer Center
  • California
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center, Fairview
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Cancer Center St. Louis Park
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Taussig Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Corpus Christi, Texas, United States, 78405
      • South Texas Institute of Cancer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Stage IIIb with malignant pleural or pericardial effusion or Stage IV (American Joint Committee on Cancer [AJCC]) NSCLC
• ECOG performance score of 0 or 1
• Adequate bone marrow, hepatic, and renal function
• New York Heart Association (NYHA) score 1-2
• Life expectancy of at least 12 weeks
• Women of child-bearing potential and men whose partners are of child-bearing potential must be willing to use an acceptable method of birth control during trial participation or are surgically sterile or women who are post-menopausal (defined as not having a menstrual cycle for greater than two years).
• The patient or patient's legal representative has the ability to understand the requirements of the trial, has provided written informed consent, and agrees to abide by the trial restrictions and to return for the required assessments.
• The patient must be able to self administer daily subcutaneous injections or his/her caregiver must be able to administer daily subcutaneous injections.

Exclusion Criteria:

• Prior chemotherapy for advanced NSCLC or the patient has received prior neoadjuvant or adjuvant chemotherapy for NSCLC in the year prior to the date of randomization
• Patients with central nervous system (CNS) metastases
• Any systemic disease precluding chemotherapy
• Chronic use of systemic corticosteroids in pharmacological doses
• Known or history of HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Contraindication to treatment with paclitaxel or carboplatin or any of the components of NOV-002
• Any known preexisting medical condition, including substance abuse, that could interfere with the patient's participation in and completion of the protocol
• Have received any investigational drug, defined as a drug for which there is no Food and Drug Administration (FDA) approved indication, within the 30 days prior to randomization
• Pregnant female or nursing mother

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: NOV-002 plus Chemotherapy; NOV-002 in combination with Paclitaxel and Carboplatin	Drug: Paclitaxel; Paclitaxel is dosed at 200 mg/m2, as a 3 hour infusion. All randomized patients will follow the established 21-day cycle of paclitaxel and carboplatin including the administration of pre-medications for these products per the package inserts. Paclitaxel and carboplatin cycles will be administered until documented disease progression or completion of 6 cycles of paclitaxel and carboplatin in the absence of response or unacceptable related toxicity, whichever comes first.; Other Names: Taxol; Abraxane; Onxol; Drug: NOV-002; Two 60 mg intravenous boli given 3 hours apart administered the day prior to the first administration of paclitaxel and carboplatin cycle one; For each nominal 21-day paclitaxel and carboplatin cycle:60 mg given intravenously on Day 1, given one hour prior to paclitaxel and carboplatinfollowed by 60 mg subcutaneously daily for the next 20 days. If there is a delay in chemotherapy cycles, the patient will continue with daily, subcutaneous administration of NOV-002 until the next cycle of chemotherapy begins Patients randomized to NOV-002 Group A, will receive NOV-002 until disease progression, unacceptable NOV-002 related toxicity, or discontinuation of paclitaxel and carboplatin, whichever comes first.; Drug: Carboplatin; Carboplatin is dosed at an area under the curve (AUC) of 6 mg/mL/min using the Calvert equation for carboplatin dosing. All randomized patients will follow the established 21-day cycle of paclitaxel and carboplatin including the administration of pre-medications for these products per the package inserts. Paclitaxel and carboplatin cycles will be administered until documented disease progression or completion of 6 cycles of paclitaxel and carboplatin in the absence of response or unacceptable related toxicity, whichever comes first. The initial dose of chemotherapy for every patient in the trial is 200 mg/m2 of paclitaxel, as a 3 hour infusion, followed by carboplatin at an area under the curve (AUC) of 6 mg/mL/min using the Calvert equation for carboplatin dosing.; Other Names: Paraplatin
Active Comparator: Group B: Chemotherapy Alone; Paclitaxel and Carboplatin	Drug: Paclitaxel; Paclitaxel is dosed at 200 mg/m2, as a 3 hour infusion. All randomized patients will follow the established 21-day cycle of paclitaxel and carboplatin including the administration of pre-medications for these products per the package inserts. Paclitaxel and carboplatin cycles will be administered until documented disease progression or completion of 6 cycles of paclitaxel and carboplatin in the absence of response or unacceptable related toxicity, whichever comes first.; Other Names: Taxol; Abraxane; Onxol; Drug: Carboplatin; Carboplatin is dosed at an area under the curve (AUC) of 6 mg/mL/min using the Calvert equation for carboplatin dosing. All randomized patients will follow the established 21-day cycle of paclitaxel and carboplatin including the administration of pre-medications for these products per the package inserts. Paclitaxel and carboplatin cycles will be administered until documented disease progression or completion of 6 cycles of paclitaxel and carboplatin in the absence of response or unacceptable related toxicity, whichever comes first. The initial dose of chemotherapy for every patient in the trial is 200 mg/m2 of paclitaxel, as a 3 hour infusion, followed by carboplatin at an area under the curve (AUC) of 6 mg/mL/min using the Calvert equation for carboplatin dosing.; Other Names: Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival during the length of the trial, length of the trial is approximately two years after last patient in	16 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Improved progression-free survival (PFS)	16 months
Higher anti-tumor overall response rate (ORR)	16 months
Less myelosuppression and improved recovery from chemotherapy-induced myelosuppression	16 months
Immunomodulation as evidenced by changes in lymphocyte subsets	16 months

Collaborators and Investigators

• Sponsor: Cellectar Biosciences, Inc.
• Investigators: Study Chair: Thomas Lynch, MD, Massachusetts General Hospital; Study Chair: Panos Fidias, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: June 29, 2006
• First Submitted That Met QC Criteria: June 29, 2006
• First Posted (Estimate): July 4, 2006

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: NSCLC; Stage IV; NSCLC Stage IV; Non Small Cell Lung Cancer (NSCLC); Stage IIIb; NSCLC Stage IIIb with malignant pleural/pericardial effusion
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: NOV002-C301